The long-term goals of this research project are to elucidate the molecular and cellular mechanisms for neuroadaptation to ethanol. Different groups of adult Drosophila will be given acute treatment with ethanol, chronic treatment, or will be withdrawn from chronic treatment. These groups will be studied in a battery of tests that measure innate and learned behaviors to gain an appreciation for the scope of behavioral neuroadaptations that occur and to quantify behavioral tolerance, sensitivity, and dependency for ethanol. Microarray analysis of the complete genome of the fly will be used to examine the changes in gene expression that occur in the brain with the ethanol treatments. RNA in situ hybridization and other techniques will be used to verify the microarray expression results and to reveal the spatial expression pattern of the ethanol-regulated genes in the brain. The morphology of some brain neurons, including mushroom body neurons, will be studied using immunohistochemistry, clonal analysis, and electron microscopy to detect and characterize the changes in cellular morphology that occur with ethanol treatment. These studies comprise a comprehensive plan to better understand the behavioral adaptations that occur with ethanol treatment and to reveal the molecular and anatomical correlates of these adaptations.